The overall objective is to explore the control of myelination in the mammalian nervous system. Studies conducted to date have established that 1) the neuron and its axon regulate the myelinating behavior of the Schwann cell and oligodendrocyte, 2) a common axonal signal for myelin formation is likely to exist both in the central (CNS) and peripheral nervous systems (PNS), 3) Schwann cells undergo atrophy and disappear after prolonged deprivation of axonal contact. Proposed studies will attempt to strengthen the idea of a common axonal signal for myelination in the CNS and PNS by determining whether regenerating optic nerve axons can stimulate peripheral myelinating cells to elaborate myelin. In a second experiment we shall attempt to create a model of the CNS-PNS transition zone in order to study the role of astrocytes in maintaining the separation of central and peripheral myelinating cells. Finally, we shall employ myelinotoxic agents to examine changes in axon and myelinating cell relationships during demyelination and remyelination.